Chronic pain affects 100 million people in the United States (U.S.) and produces annual costs up to $635 billion. While pain affects all segments of the population, racial and ethnic minorities in the U.S., particularly African Americans (AAs) experience more frequent, severe and disabling chronic pain compared to their non-Hispanic white (NHW) counterparts. While multiple factors inevitably contribute, ethnic group differences in central pain processing represent a potentially important determinant of greater clinical pain among AAs. During the previous funding cycle we found that African Americans (AA) with knee osteoarthritis (OA) reported significantly greater OA-related pain and disability than their non-Hispanic white (NHW) counterparts. Moreover, quantitative sensory testing indicated greater generalized pain facilitation and diminished pain inhibition among AA compared to NHW with and without knee OA. In addition, we observed ethnic differences in pain-related psychosocial and biological measures, which at least partially mediated ethnic group differences in pain sensitivity. However, our current findings provide indirect and cross-sectional evidence regarding ethnic group differences in central pain processing and their relationship to clinical pain. Moreover, ethnic group differences in the progression of both clinical symptoms and altered central pain processing over time, and the predictors thereof, have heretofore not been investigated. Therefore, the overarching goal of the proposed studies is to elucidate the mechanisms underlying ethnic group differences in knee OA-related pain by directly and prospectively assessing the progression and predictors of clinical pain and disability as well as altered central pain processing among middle-aged and older AA and NHW with symptomatic knee OA. Specifically, we propose to characterize ethnic group differences in clinical symptoms, systemic inflammation, psychosocial functioning and pain-related central nervous system (CNS) structure and function at baseline and over a two year follow-up period among older AA and NHW with symptomatic knee OA. We also propose to identify biopsychosocial predictors of ethnic group differences in the progression of both OA-related clinical symptoms as well as changes in pain- related CNS structure and function over the two-year follow-up period. This study will be the first to directly investigate ethnic group differences in central pain processing and to prospectively characterize the progression and biopsychosocial predictors of longitudinal changes in clinical symptoms and pain-related CNS structure and function in OA-related pain. The findings will provide novel and important information regarding the mechanisms underlying ethnic group differences in pain.